Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study.

BACKGROUND: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. METHODS: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.

Thromboembolic events in patients who received adjuvant chemotherapy for gastric cancer: a single-center retrospective study.

BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.

Analysis of thromboembolic events in patients with non-small cell lung cancer who received adjuvant chemotherapy: single-center real-world data.

Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.

Clinical findings, viral load, and outcomes of COVID-19: Comparison of patients with negative and positive initial chest computed tomography.

Reports detailing the clinical characteristics, viral load, and outcomes of patients with normal initial chest CT findings are lacking. We sought to compare the differences in clinical findings, viral loads, and outcomes between patients with confirmed COVID-19 who initially tested negative on chest CT (CT negative) with patients who tested initially positive on chest CT (CT positive). The clinical data, viral loads, and outcomes of initial CT-positive and CT-negative patients examined between January 2020 and April 2020 were retrospectively compared. The efficacy of viral load (cyclic threshold value [Ct value]) in predicting pneumonia was evaluated using receiver operating characteristic (ROC) curve and area under the curve (AUC). In total, 128 patients underwent initial chest CT (mean age, 54.3 ± 19.0 years, 50% male). Of those, 36 were initially CT negative, and 92 were CT positive. The CT-positive patients were significantly older (P < .001) than the CT-negative patients. Only age was significantly associated with the initial presence of pneumonia (odds ratio, 1.060; confidence interval (CI), 1.020-1-102; P = .003). In addition, age (OR, 1.062; CI, 1.014-1.112; P = .011), fever at diagnosis (OR, 6.689; CI, 1.715-26.096; P = .006), and CRP level (OR, 1.393; CI, 1.150-1.687; P = .001) were significantly associated with the need for O2 therapy. Viral load was significantly higher in the CT-positive group than in the CT-negative group (P = .017). The cutoff Ct value for predicting the presence of pneumonia was 27.71. Outcomes including the mean hospital stay, intensive care unit admission, and O2 therapy were significantly worse in the CT-positive group than in the CT-negative group (all P < .05). In conclusion, initially CT-negative patients showed better outcomes than initially CT-positive patients. Age was significantly associated with the initial presence of pneumonia, and viral load may help in predicting the initial presence of pneumonia.

Clinical and Laboratory Factors Associated with Symptom Development in Asymptomatic COVID-19 Patients at the Time of Diagnosis.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

Peer support for smoking cessation: a protocol of systematic review and meta-analysis.

BACKGROUND: Peer-support programs are a useful social support strategy for populations trying to quit smoking who are willing to maintain smoking abstinence. This study is a protocol for a systematic review and meta-analysis to assess the effectiveness of peer support for smoking cessation. METHODS: This protocol will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.2. We will conduct a comprehensive search in the Cochrane Central Register of Controlled Trials, ovidEmbase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ovidMEDLINE, Google Scholar, and Open Grey, as well as the Trials Register of Promoting Health Interventions in EPPI-Centre, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and reference lists of included papers. The review will include randomized controlled trials of peer support interventions aimed to stop smoking in any population. Two reviewers will independently screen and select relevant studies. Version 2 of the Cochrane tool that assesses risk of bias in randomized trials will be used to assess the risk of bias in the included studies. The primary outcomes will be defined as the tobacco abstinence rate and adverse events. If a quantitative synthesis is not appropriate, a synthesis without meta-analysis will be undertaken. DISCUSSION: This review will provide the best available evidence regarding the effects of peer support interventions to quit smoking. The results from this study will help to inform healthcare providers on the optimal peer support intervention modalities such as intensity, delivery methods, type of support provider, and duration of the intervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196288.

A comprehensive study of deaths due to exposure to humidifier disinfectant in Korea: focusing on medical records, assessment of exposure to humidifier disinfectants, and causes of death.

OBJECTIVES: We aimed to determine the characteristics of the deceased victims of deaths caused by exposure to humidifier disinfectants, and present the distribution of the victims' data submitted for damage application, demographic characteristics, imaging findings, characteristics of humidifier disinfectant exposure, and distribution of the causes of death. METHODS: An integrated database of victims was established using the medical records data of 1,413 victims submitted during the application for death damage caused by exposure to humidifier disinfectants, and the demographic characteristics, medical records, imaging findings, exposure characteristics, and cause of death were examined. RESULTS: The average numbers of data submissions of each applicant for death damage were 3.0 medical use records. A total of 608 (43.0%) victims had more than one finding of acute, subacute, or chronic interstitial lung diseases. The average daily and cumulative use times of the victims were 14.40 and 24,645.81 hours, respectively, indicating greater exposure in this group than in the survivors. The humidifier disinfectants' components comprised polyhexamethylene guanidine (72.8%), chloromethylisothiazolinone/methylisothiazolinone (10.5%), other components (15.0%), and oligo-[2-(2-ethoxy)-ethoxyethyl] guanidine chloride (1.5%). The components' distribution was 67.8% for single-component use, which was higher than that in the survivors (59.8%). The distribution of the causes of death were: respiratory diseases (54.4%), neoplasms (16.8%), and circulatory diseases (6.3%). Other interstitial lung diseases (65.5%) were the most common cause of death among those who died due to respiratory diseases. CONCLUSIONS: Careful discussions of appropriate remedies should be conducted based on a comprehensive understanding of the characteristics of the deceased victims, considering their specificities and limitations.

Interferon-γ-Inducible Chemokines as Prognostic Markers for Lung Cancer.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80-0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I-III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

TB Antigen-Stimulated CXCR3 Ligand Assay for Diagnosis of Tuberculous Lymphadenitis.

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.

Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data.

BACKGROUND: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. METHODS: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. RESULTS: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. CONCLUSIONS: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.

e-Health Interventions for Community-Dwelling Type 2 Diabetes: A Scoping Review.

Background: Because type 2 diabetes mellitus is a critical health problem with increasing incidence, prevalence, and complications worldwide, e-health has been widely utilized for management in type 2 diabetes. Introduction: This scoping review of meta-analyses and systematic reviews on e-health interventions aimed to examine service platforms, program types, outcomes, current status of research activities, research gaps, and the effectiveness of type 2 diabetes self-care management among community-dwelling adults. Materials and Methods: Arksey and O'Malley's method was adopted for this review. The Ovid MEDLINE and Ovid EMBASE databases were searched from inception until April 2018. Two reviewers independently screened, selected, and charted studies using a piloted charting form. Discrepancies were resolved by consensus, and results were collated, summarized, and thematically analyzed. Results: The final studies (N = 81) related to e-health interventions included systematic reviews/meta-analyses on clinical effectiveness (n = 64), usability (n = 14), and behavioral outcomes (n = 47). The commonest e-health intervention subtypes for type 2 diabetes care were patient monitoring (53/163, 32.5%), treatment adherence (50/163, 30.7%), and diabetes-related advice/education (34/163, 20.9%). Mobile devices were most often used to provide e-health services (57/142, 40.1%), followed by the internet (41/142, 28.9%). The e-health strategy that was effective in controlling blood glucose in type 2 diabetes patients was a multimodal intervention comprising treatment advice or education, treatment adherence or reminder methods, and patient monitoring. Treatment adherence or reminder methods and/or patient monitoring showed behavioral effects, but the usability of e-health interventions was controversial. Conclusions: We suggest that e-health intervention should be complex intervention including treatment advice/education, patient monitoring, and treatment adherence or reminder methods.

Differences in Vancomycin Clearance between Trauma and Medical Intensive Care Unit Patients.

BACKGROUND: To identify the differences in the vancomycin pharmacokinetics between multiple trauma patients and medically ill patients in the intensive care unit (ICU) stratified by the use of continuous renal replacement therapy (CRRT), and the factors affecting vancomycin clearance (CLvan). MATERIALS AND METHODS: All the included patients received at least three consecutive doses of vancomycin, then, therapeutic drug monitoring was conducted. Patients' serum vancomycin trough levels and other clinical variables were identified retrospectively. The vancomycin pharmacokinetics and associated factors were compared and analyzed between trauma ICU (TICU) and medical ICU (MICU) patients. RESULTS: In the non-dialyzed group, the CLvan was higher among the TICU patients than the MICU patients. However, in the continuous renal replacement therapy group, there was no significant difference in the CLvan between the multiple trauma and medically ill patients. The only factor associated with CLvan in the non-dialyzed group was creatinine clearance; none of the factors was associated with CLvan in the CRRT group. CONCLUSION: In the case of non-dialyzed patients in the TICU, vancomycin dosages must be adjusted, depending on the patient's actual body weight changes. In the case of patients undergoing CRRT in both ICUs, vancomycin can be infused with fixed doses regardless of the patients' characteristics.

Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma.

OBJECTIVES: Radon, a natural radiation, is the leading environmental cause of lung cancer in never-smokers. However, the radon exposure impact on the mutational landscape and tumor mutation burden (TMB) of lung cancer in never-smokers has not been explored. The aim of this study was to investigate the mutational landscape of lung adenocarcinoma in never-smokers who were exposed to various degrees of residential radon. MATERIALS AND METHODS: To investigate the effect of indoor radon exposure, we estimated the cumulative exposure to indoor radon in each house of patients with lung cancer with a never-smoking history. Patients with at least 2 year-duration of residence before the diagnosis of lung adenocarcinoma were included. Patients were subgrouped based on the median radon exposure level (48 Bq/m3): radon-high vs. radon-low and targeted sequencing of tumor and matched blood were performed in all patients. RESULTS: Among 41 patients with lung adenocarcinoma, the TMB was significantly higher in the radon-high group than it was in the radon-low group (mean 4.94 vs. 2.6 mutations/Mb, P = 0.01). The recurrence rates between radon-high and radon-low group did not differ significantly. Mutational signatures of radon-high tumors showed features associated with inactivity of the base excision repair and DNA replication machineries. The analysis of tumor evolutionary trajectories also suggested a series of mutagenesis induced by radon exposure. In addition, radon-high tumors revealed a significant protein-protein interaction of genes involved in DNA damage and repair (P < 0.001). CONCLUSIONS: Indoor radon exposure increased the TMB in never-smoker patients with lung adenocarcinoma and their mutational signature was associated with defective DNA mismatch repair.

Impact of body fat distribution on long-term clinical outcomes after drug-eluting stent implantation.

BACKGROUND AND OBJECTIVE: The distribution of body fat is closely related to cardiovascular disease and outcomes, although its impact on patient prognosis after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) has not been evaluated. We investigated the impact of truncal fat distribution on long-term clinical outcomes after DES treatment. METHODS: In 441 DES-treated patients, dual energy X-ray absorptiometry was performed to assess total and regional body fat distribution after index PCI. The ratio of truncal fat to total body fat mass (%FMtrunk/FMtotal) was calculated as a representative parameter for truncal fat distribution. The primary endpoint was major adverse cardiac events (MACE), a composite of ischemia-driven target vessel revascularization (TVR), non-procedural myocardial infarction, cardiac death at 5 years. RESULTS: During the median follow-up duration of 1780 days, MACE occurred in 22.0% of patients, with the highest-quartile group of %FMtrunk/FMtotal having a higher rate than the lowest quartile group (27.8% vs. 15.3%; log rank p = 0.026). The difference was driven by a higher rate of ischemia-driven TVR (25.9% vs. 9.9%; log rank p = 0.008). In multivariable Cox regression analyses, %FMtrunk/FMtotal was independently associated with MACE (hazard ratio: 1.075; 95% CI: 1.022-1.131; p = 0.005), but body mass index (BMI) was not. CONCLUSIONS: In DES-treated patients, truncal fat distribution is associated with unfavorable clinical outcomes and is more clinically relevant than BMI.

Methodology for Developing Evidence-Based Clinical Imaging Guidelines: Joint Recommendations by Korean Society of Radiology and National Evidence-Based Healthcare Collaborating Agency.

This paper is a summary of the methodology including protocol used to develop evidence-based clinical imaging guidelines (CIGs) in Korea, led by the Korean Society of Radiology and the National Evidence-based Healthcare Collaborating Agency. This is the first protocol to reflect the process of developing diagnostic guidelines in Korea. The development protocol is largely divided into the following sections: set-up, process of adaptation, and finalization. The working group is composed of clinical imaging experts, and the developmental committee is composed of multidisciplinary experts to validate the methodology. The Korean CIGs will continue to develop based on this protocol, and these guidelines will act for decision supporting tools for clinicians as well as reduce medical radiation exposure.

Evaluation report on the causal association between humidifier disinfectants and lung injury.

OBJECTIVES: As of November 2011, the Korean government recalled and banned humidifier disinfectants (HDs) from the market, because four case-control studies and one retrospective epidemiological study proved the association between HDs and lung injury of unknown cause. The report reviewed the causal role of HDs in lung injury based on scientific evidences. METHODS: A careful examination on the association between the HDs and lung injury was based on the criteria of causality inference by Hill and the US Surgeon General Expert Committee. RESULTS: We found that all the evidences on the causality fulfilled the criteria (strength of association, consistency, specificity, temporality, biologic gradient, plausibility, coherence, experiment, analogy, consideration of alternative explanations, and cessation of exposure), which proved the unknown cause lung injury reported in 2011 was caused by the HDs. In particular, there was no single reported case of lung injury since the ban in selling HDs in November 2011 as well as before the HDs were sold in markets. CONCLUSIONS: Although only a few epidemiological studies in Korea have evaluated the association between lung injury and the use of HDs, those studies contributed to proving the strong association between the use of the HDs and lung injury, based on scientific evidence.

The relationship between coronary atherosclerosis and body fat distribution measured using dual energy X-ray absorptiometry.

OBJECTIVE: Body fat distribution is closely related to cardiovascular diseases. We aimed to evaluate the relationship between truncal fat distribution and the extent of coronary atherosclerosis. METHODS: Total body fat and regional body fat distributions were measured using dual-energy X-ray absorptiometry (DXA) in 746 Korean patients who underwent coronary angiography. The ratios of truncal fat mass to total body fat mass (FMtrunk/FMtotal), truncal fat mass to fat mass in both legs (FMtrunk/FMleg) and truncal fat mass to fat mass in both arms (FMtrunk/FMarm) were calculated as representative parameters for truncal fat accumulation. The extent of coronary atherosclerosis was assessed using the Gensini score. RESULTS: The mean Gensini score of the patients was 21.3 ± 24.4. FMtrunk/FMtotal, FMtrunk/FMleg and FMtrunk/FMarm revealed positive correlations with the Gensini score (r = 0.242, p < 0.001; r = 0.219, p < 0.001; r = 0.133, p < 0.001, respectively). In contrast, body mass index (BMI) and total body fat mass did not correlate with the Gensini score. On multiple regression analysis, FMtrunk/FMtotal was associated with the Gensini score independently of age, gender, BMI and major risk factors of coronary heart disease (B = 0.039, p < 0.001). CONCLUSION: Truncal fat distribution is associated with the extent of coronary atherosclerosis and more clinically relevant to that compared with total body fat or BMI in Korean patients.

An updated review of case-control studies of lung cancer and indoor radon-Is indoor radon the risk factor for lung cancer?

Lung cancer is a leading cause of cancer-related death in the world. Smoking is definitely the most important risk factor for lung cancer. Radon ((222)Rn) is a natural gas produced from radium ((226)Ra) in the decay series of uranium ((238)U). Radon exposure is the second most common cause of lung cancer and the first risk factor for lung cancer in never-smokers. Case-control studies have provided epidemiological evidence of the causative relationship between indoor radon exposure and lung cancer. Twenty-four case-control study papers were found by our search strategy from the PubMed database. Among them, seven studies showed that indoor radon has a statistically significant association with lung cancer. The studies performed in radon-prone areas showed a more positive association between radon and lung cancer. Reviewed papers had inconsistent results on the dose-response relationship between indoor radon and lung cancer risk. Further refined case-control studies will be required to evaluate the relationship between radon and lung cancer. Sufficient study sample size, proper interview methods, valid and precise indoor radon measurement, wide range of indoor radon, and appropriate control of confounders such as smoking status should be considered in further case-control studies.

Erratum to: An updated review of case-control studies of lung cancer and indoor radon-Is indoor radon the risk factor for lung cancer?

[This corrects the article DOI: 10.1186/s40557-016-0094-3.].

A newly developed tool for classifying study designs in systematic reviews of interventions and exposures showed substantial reliability and validity.

OBJECTIVE: To develop a study Design Algorithm for Medical Literature on Intervention (DAMI) and test its interrater reliability, construct validity, and ease of use. STUDY DESIGN AND SETTING: We developed and then revised the DAMI to include detailed instructions. To test the DAMI's reliability, we used a purposive sample of 134 primary, mainly nonrandomized studies. We then compared the study designs as classified by the original authors and through the DAMI. Unweighted kappa statistics were computed to test interrater reliability and construct validity based on the level of agreement between the original and DAMI classifications. Assessment time was also recorded to evaluate ease of use. RESULTS: The DAMI includes 13 study designs, including experimental and observational studies of interventions and exposure. Both the interrater reliability (unweighted kappa = 0.67; 95% CI [0.64-0.75]) and construct validity (unweighted kappa = 0.63, 95% CI [0.52-0.67]) were substantial. Mean classification time using the DAMI was 4.08 ± 2.44 minutes (range, 0.51-10.92). CONCLUSIONS: The DAMI showed substantial interrater reliability and construct validity. Furthermore, given its ease of use, it could be used to accurately classify medical literature for systematic reviews of interventions although minimizing disagreement between authors of such reviews.